P1, N=330, Recruiting, I-Mab Biopharma US Limited | N=168 --> 330 | Trial completion date: Dec 2026 --> Dec 2027 | Trial primary completion date: Dec 2025 --> Dec 2026

P3, N=500, Recruiting, Astellas Pharma Global Development, Inc. | Trial completion date: Dec 2029 --> Sep 2028 | Trial primary completion date: Dec 2029 --> Sep 2028

Its expression was rarely observed in other histological types of lung cancer. CLDN18.2 is frequently expressed in IMAs but rarely in other major lung cancer subtypes, suggesting that zolbetuximab may represent a promising targeted therapy for IMA.

We performed [89Zr]Zr-zolbetuximab immuno-PET imaging to quantify and localized CLDN18.2 expression in vivo, comparing uptake with [89Zr]Zr-trastuzumab in matched human epidermal growth factor receptor 2-positive patient-derived xenograft models. These findings outline a clinically relevant roadmap for CLDN18.2 radiotheranostics in which imaging enables patient selection and dosimetry, therapy delivers targeted tumor control, and rational combinations with chemotherapy or immunotherapy may further extend efficacy. Ultimately, this approach could make antibody-based radiopharmaceuticals a transformative modality in gastric cancer.

P2, N=180, Recruiting, I-Mab Biopharma US Limited

CLDN18.2 has become a major new target in gastric cancer targeted therapy. Its clinical trials and development are advancing quickly, with various types of drugs available. In the future, more released data may make treatment strategies better and give new treatment options to gastric cancer patients.

Pooled analysis of the SPOTLIGHT and GLOW phase III trials, involving 1072 patients with locally advanced or metastatic gastric/gastroesophageal junction (GC/GEJ) adenocarcinoma positive for claudin18.2 (CLDN18.2) and negative for HER2, showed that zolbetuximab combined with chemotherapy significantly improved progression-free survival (PFS) compared to placebo (HR = 0.72; 95% CI, 0.61-0.84)...Additionally, CLDN18.2 knockdown down-regulated minichromosome maintenance (MCM) proteins, particularly MCM2 and MCM5, and decreased phosphorylation of ERK, CDK, and MCM2 in GC cells. These findings provide a theoretical basis for the future selection of advantageous populations for CLDN18.2-targeted therapy and combination therapy strategies.

P=N/A, N=70, Recruiting, European Institute of Oncology

P1/2, N=200, Recruiting, UZ Leuven

CLDN18.2, as an emerging target, has been proven in multiple studies to have potential in the treatment of advanced gastric cancer, with drugs targeting CLDN18.2, such as Zolbetuximab, already approved, opening new pathways for precision treatment. Furthermore, research on targets such as FGFR2b, MET, DKK1, and TROP2 continues, aiming to offer personalized treatment plans for patients with different biomarker profiles. Although the current biomarkers have certain limitations in treatment, the continuous discovery of new targets and the deepening of clinical research hold great promise for precision treatment of gastric cancer and are expected to significantly improve the prognosis of advanced gastric cancer patients.

P3, N=565, Active, not recruiting, Astellas Pharma Global Development, Inc. | Trial completion date: Mar 2026 --> Sep 2026

P3, N=507, Active, not recruiting, Astellas Pharma Global Development, Inc. | Trial completion date: Mar 2026 --> Sep 2026